Tobacco use accounts for over 400,000 U.S deaths each year due to cardiovascular disorders, cancers, and other health problems. Much of this morbidity and mortality is attributable to the toxicants that cigarette smokers inhale like carcinogens, carbon monoxide (CO), and the dependence-producing drug nicotine. Cigar smoking is also linked to cancer and other health disorders, and cigar smoke contains many of the same toxicants as cigarette smoke. Unfortunately, unlike cigarette smoking, cigar smoking has not declined in recent years, especially among young adults who are the most frequent users of the cigarillo - a short, slender cigar comprised of a tobacco leaf wrapper, a reconstituted tobacco binder, and tobacco leaf filler. Cigarillos appeal to young consumers because of the availability of enticing flavors like grape, cherry, and vanilla, and the sweet aroma produced by cigarillos when smoked. Young adult use of cigarillos has also been spurred by perceptions of reduced harm of cigarillos compared to cigarettes. In fact, there is a widely-held belief that exposure to cigarillo smoke toxicants can be reduced by removing the reconstituted tobacco binder through a modification process known as hyping. Perhaps most concerning is the scientific community knows very little about the toxicant exposure and effects of cigarillos and its various forms of use (i.e., original or modified forms). Understanding cigarilo use involves a transdisciplinary approach that addresses cigarillo smoke toxicant yield, cigarillo user toxicant exposure, and the cardiovascular and subjective effects associated with cigarillo use directly. The specific aims of this proposal are to: (1) Compare the toxicant yield of original and modified cigarillos, (2) Investigate toxicant exposure and effects of original and modified cigarillos in the laboratory, and (3) Examine toxicant exposure and effect when participants smoke original or modified cigarillos in their natural environment. Notable is that similar information regarding the effects of cigarettes has been used to inform prevention and cessation interventions and to guide recent legislative efforts in tobacco control (i.e., Family Smoking Prevention and Tobacco Control Act, 2009). This project is consistent with NCI's Areas of Intensified Scientific Investigation (Connecting the Nation's Cancer Community: An Annual Plan and Budget Proposal for FY2011) to support the U.S. FDA's regulation of tobacco products by developing methods and measures for determining the impact of product ingredient changes. In this case, user-initiated modifications to reduce exposure to harmful ingredients in cigarillo smoke. This proposal uses a combination of newly-developed, analytical laboratory and clinical methods to address an emerging tobacco use phenomenon.